The present invention relates to a calcium ion selective electrode of a polymeric support membrane type suitable for the measurement of the concentration of a calcium ion in a living body fluid such as blood.
Ions which are cations contained in a living body fluid, particularly blood, and frequently measured in the field of clinical tests are sodium, potassium, lithium and calcium ions. Among them, the sodium ion which is contained in the highest concentration, having a normal value of concentration of 135 to 145 mmol/l.
On the other hand, the normal value of calcium ion concentration is 1 to 2 mmol/l, i.e., about two figures lower than that of the sodium ion. The measurement of the calcium ion has been regarded as clinically important for the diagnosis of thyroid gland function, never excitement and transfer function. From this point of view, it will be understood that whether or not the calcium ion can accurately be measured is an important key to the evaluation of the health condition based on the calcium ion concentration.
One of the methods of measuring the ion concentration of a living body fluid is an ion selective electrode method, and in recent years this method has come into wide use in the field of clinical tests. However, in order to realize an accurate measurement, it is necessary to eliminate a primary factor of error based on the influence of an interfering substance, etc., on the electrode.
If there is a coexistent ion, the relationship between the electrode output (E) and the activity (substantially equal to the concentration) when an intended ion is measured with an ion selective electrode can be expressed by the following equation (I): EQU E=E.sub.0 +(RT/Z.sub.i F) log[a.sub.i +.SIGMA.K.sub.ij (a.sub.j).sup.z.sbsp.i.sup./z.sbsp.j (I)
where E.sub.0 is the standard potential, R is the gas constant, T is the absolute temperature, F is the Faraday constant, a and z are the activity and valence of the intended ion (i) and the interfering ion (j), respectively, and K.sub.ij is the selectivity factor.
RT/z.sub.i F is called a slope sensitivity and serves as a measure of whether or not the ion selective electrode is satisfactory.
The slope sensitivity (29.58 mV/dec. at 25.degree. C.) of a selective electrode (hereinafter referred to simply as the "electrode") which selects a calcium ion as a divalent ion and measures the ion concentration is one half of the slope sensitivity (59.16 mV/dec. at 25.degree. C.) of an electrode for a sodium ion as a monovalent ion.
When the calcium ion concentration is measured by the ion selective electrode method, the selectivity of the electrode is lower than that of the electrode for the sodium ion and further as described above the concentration to be measured is very low, which makes it more difficult to conduct an accurate measurement.
An ion sensitive membrane is essential to the ion selective electrode. This sensitive membrane comprises a sensitive substance selectively responsive to the intended ion, a plasticizer which plasticizes and serves also as a solvent for the membrane, and a matrix material comprising a polymeric substance such as polyvinyl chloride. The characteristics of the electrode depend mainly upon the sensitive substance and plasticizer.
In order to realize an accurate measurement, it is necessary to:
(1) lower the selectivity factor, K.sub.ij, of the ion selective electrode,
(2) present the interference by a lipophilic anion as shown in the equation (II) described later, and
(3) enhance the responsiveness of the electrode.
Although the selectivity factor described in the above item (1) is substantially determined by the ratio of the stability constant in a complex forming reaction of the sensitive substance with the intended ion, it essentially depends upon the sensitive substance. On the other hand, the properties of the plasticizer affect the interference by a lipophilic anion and the responsiveness of the electrode.
A neutral carrier and an ion exchanger have been used as the sensitive substance for the calcium ion selective electrode. When the sensitive substance is the former one, ether compounds, such as o-nitrophenyl octyl ether (dielectric constant.apprxeq.24), have been used as the plasticizer [see Anal. chem. 1986, 58, 2282-2285 "Neutral Carrier Based Ca.sup.2+ --Selective Electrode with Detection Limit in the Sub-Nanomolar Range"], while when the sensitive substance is the latter one, plasticizers having relatively higher dielectric constants, such as esters of phosphoric acid such as di-n-octyl phenyl phosphate, have been used alone.
The present inventors have made various studies on the conventional ether compounds and other plasticizers in connection with the plasticizer for the sensitive membrane of a calcium ion selective electrode wherein use is made of a neutral carrier type of sensitive substance and, as a result, have found that a calcium ion selective electrode wherein use is made of a neutral carrier type of sensitive substance is susceptible to the interference by a lipophilic anion, with a different extent of influence depending also upon the plasticizer, and has a responsiveness susceptible to the properties of the plasticizer.
The above-described conventional sensitive membrane for a calcium ion selective electrode had problems with, for example, the sensitivity and responsiveness of the electrode.